Study on the therapeutic effect of Kirschner wire tension band combined with anchor cross-stitch technique in the treatment of comminuted patellar inferopolar fractures.

PURPOSES: Fractures of the inferior patellar pole, unlike other patellar fractures, present challenges for traditional surgical fixation methods. This article introduces the clinical technique and outcomes of using Kirschner wire tension band combined with anchor screw cross-stitch fixation for comminuted inferior patellar pole fractures. METHODS: This retrospective case series study included 14 patients with comminuted inferior patellar pole fractures treated at our institution from September 1, 2020, to April 30, 2022. All patients underwent surgery using the Kirschner wire tension band with anchor screw cross-stitch technique. Follow-up assessments involved postoperative X-rays to evaluate fracture healing, as well as clinical parameters such as healing time, Visual Analog Scale (VAS) scores, range of motion (ROM), and Bostman scores. RESULTS: All patients were followed for an average of over 12 months, with no cases of internal fixation failure. Knee joint stability and function were excellent. X-rays revealed an average healing time of approximately 10.79 ± 1.53 weeks, hospitalization lasted 5.64 ± 1.15 days, surgery took approximately 37.86 ± 5.32 minutes, and intraoperative blood loss was 33.29 ± 8.15 ml. One patient experienced irritation from the internal fixation material. At the final follow-up, the Bostman score averaged 28.29 ± 0.83, knee joint flexion reached 131.07° ± 4.88°, all patients achieved full knee extension, and the VAS score was 0.36 ± 0.63. CONCLUSION: Kirschner wire tension band with anchor screw cross-stitch fixation for comminuted inferior patellar pole fractures delivered satisfactory clinical outcomes. This surgical method, characterized by its simplicity and reliability, is a valuable addition to clinical practice.

A review of 10 patients treated with the masquelet technique and microsurgical technique combined for Gustilo type III open tibial fractures.

BACKGROUND: Open tibial fractures often include severe bone loss and soft tissue defects and requires complex reconstructive operations. However, the optimal treatment is unclear. METHODS: This retrospective study enrolled patients with Gustilo type III open tibial fractures from January 2018 to January 2021 to assess the clinical utility of Masquelet technique together with microsurgical technique as a combined strategy for the treatment of open tibial fractures. The demographics and clinical outcomes including bone union time, infection, nonunion and other complications were recorded for analysis. The bone recovery quality was evaluated by the AOFAS Ankle-Hindfoot Scale score and the Paley criteria. RESULTS: We enrolled 10 patients, the mean age of the patients and length of bone defects were 31.7 years (range, 23-45 years) and 7.5 cm (range, 4.5-10 cm) respectively. Bone union was achieved for all patients, with an average healing time of 12.2 months (range, 11-16 months). Seven patients exhibited a bone healing time of less than 12 months, whereas 3 patients exhibited a bone healing time exceeding 12 months. No significant correlation was found between the length of bone loss and healing time. In addition, no deep infection or nonunion was observed, although 2 patients experienced wound fat liquefaction with exudates and 1 patient presented with a bloated skin flap. The average AOFAS Ankle-Hindfoot Scale score was 80.5 (range, 74-85), and all patients were evaluated as good or exellent based on the Paley criteria. CONCLUSIONS: Our study indicated that the use of the Masquelet technique and the microsurgical technique as a combined strategy is safe and effective for the treatment of Gustilo type III open tibial fractures.

Modulation of the microRNA-6089/E2F transcription factor2 axis by querceting: implications for osteoblast viability, proliferation, migration, and osteogenic differentiation in fracture healing.

Quercetin is widely distributed in plants as a flavonol compound with multiple biological activities. It has been found that quercetin can regulate bone homeostasis through multiple pathways and targets. This study investigated the role and specific molecular mechanisms of quercetin in regulating osteoblast viability, proliferation, migration and osteogenic differentiation. A mouse model of traumatic fracture was established and then 100 mg/kg quercetin corn oil suspension was gavaged at the same time every day for 28 days. miR-6089 and E2F transcription factor 2 (E2F2) expression levels in mice were measured. Fracture healing in mice was observed. MC3T3-E1 cells were transfected with plasmids targeting miR-6089 and E2F2, and cell viability, proliferation, migration, apoptosis, and osteogenic differentiation were determined. The targeting relationship between miR-6089 and E2F2 was verified. In vivo experiments showed that quercetin significantly increased osteocalcin (OCN) expression (P<0.05) and promoted fracture healing in traumatic fracture (TF) mice. miR-6089 expression was down-regulated (P<0.05) and E2F2 expression was up-regulated (P<0.05) in TF mice. Quercetin promoted miR-6089 expression and inhibited E2F2 expression (both P<0.05). In vitro results showed that quercetin promoted miR-6089 expression and inhibited E2F2 expression in a dose-dependent manner (both P<0.05). Quercetin dose-dependently promoted MC3T3-E1 cell viability, proliferation, migration, and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). Up-regulating miR-6089 further promoted MC3T3-E1 cell viability, proliferation, migration and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). miR-6089 targeted and regulated E2F2 expression. Up-regulating E2F2 attenuated the promoting effect of up-regulated miR-6089 on MC3T3-E1 cell viability, proliferation, migration, osteogenic differentiation, and inhibition of apoptosis (all P<0.05). We conclude that quercetin enhances osteoblast viability, proliferation, migration, and osteogenic differentiation by modulating the miR-6089/E2F2 axis, thereby promoting fracture healing.

Achieving Bone Healing Non-Operatively in Humeral Fractures in Two Patients with Risk Factors for Nonunion Utilizing a Specialized Orthosis.

We report the treatment of two patient with humeral fractures with one or more risk factors for nonunion. The first patient was elderly with a previously diagnosed central nervous sys-tem injury. The second elderly patient previously sustained a cerebral vascular accident affecting the fractured arm. The fracture was oblique in the proximal third of the humerus. We achieved bone healing non-operatively utilizing a spe-cialized plastic orthosis that included a deforming element made of dense foam. This device asymmetrically increases the soft tissue pressure around the fracture.

Effectiveness of teriparatide in in improving healing rates and bone-turnover markers of osteoporotic hip fracture: a meta-analysis.

Objective: To evaluate the effect of subcutaneous teriparatide therapy on fracture healing rate and change in bone mass density in osteoporotic hip fractures. METHODS: The meta-analysis was done from September to December 2022, and comprised literature search on Wanfang, CNKI, VIP, PubMed, Embase, Cochrane Library, and Web of Science databases from the establishment of the respective database till December 2022. The relevant journals of the library of Macao University of Science and Technology, China, were manually searched for randomised controlled trials of teriparatide in the treatment of osteoporotic hip fractures. The shortlisted studies were subjectd to Cochrane Risk of Bias tool and the Jadad Rating Scale. Meta-analysis was done using the RevMan 5.4 software provided by the Cochrane Collaboration Network. Fracture healing rate and bone mineral density were the primary outcome measures, while mortality, adverse events, malformations, complications, subsequent fractures, timed-up-and-go test, visual analogue scale score, and procollagen type I N-terminal propeptide were the secondary outcome measures. RESULTS: Of the 1,094 articles retrieved, 8(0.7%) randomised controlled trials were analysed. There were 744 patients; 372(50%) in the teriparatide group and 372(50%) in the control group. Fracture healing rate was not significantly different (p=0.82), while bone mineral density was significantly different between the groups (p<0.001). Mortality, adverse events, deformity, and complications were not significantly different (p>0.05), while subsequent fractures, timed-up-and-go score, visual analogue scale score and procollagen type I N-terminal propeptide were significantly different between the groups (p<0.05). Conclusion: The literature did not support teriparatide's ability to improve the healing rate of osteoporotic hip fractures, or to reduce mortality, adverse events, malformations, and complications. In addition, teriparatide could increase bone mineral density of osteoporotic hip fractures and the procollagen type I N-terminal propeptide value, alleviate hip pain, and reduce subsequent fracture rates. This trial is registered with PROSPERO with registration number CRD42022379832.

Open Reduction and Internal Fixation for Supination-External Rotation Type IV Ankle Fractures by Means of Anterolateral and Posterolateral Approaches.

BACKGROUND: The present study aimed to analyze and compare the efficacy of the anterolateral and posterolateral approaches for surgical treatment of supination-external rotation type IV ankle fractures. METHODS: This retrospective study enrolled 60 patients (60 feet) with supination-external rotation type IV ankle fractures, including 30 patients (30 feet) treated by means of the anterolateral approach and 30 patients (30 feet) treated by means of the posterolateral approach. Postoperative clinical efficacy was compared between the groups based on operation time, intraoperative blood loss, postoperative complications, fracture healing time, visual analog scale scores, Short Form-36 Health Survey scores, and American Orthopedic Foot and Ankle Society scores. Comparisons between the two groups were performed using independent-samples t tests and analyses of variance. Intragroup differences were compared using paired t tests, and the χ2 test was used to compare categorical variables. RESULTS: All 60 included patients completed follow-up ranging from 12 to 18 months (mean duration, 14.8 ± 3.5 months). Although baseline characteristics were similar in the two groups, there were significant differences in operation time (86.73 ± 17.44 min versus 111.23 ± 10.05 min; P < .001) and intraoperative blood loss (112.60 ± 25.05 mL versus 149.47 ± 44.30 mL; P < .001). Although fracture healing time (10.90 ± 0.66 weeks versus 11.27 ± 0.94 weeks; P = .087) was shorter in the anterolateral group than in the posterolateral group, the difference was not significant. Postoperative complications occurred in one and three patients in the anterolateral and posterolateral approach groups, respectively. Visual analog scale scores were significantly lower in the anterolateral group than in the posterolateral group (1.43 ± 0.50 versus 1.83 ± 0.75; P = .019), although there was no significant difference in Short Form-36 Health Survey scores between the groups (73.63 ± 4.07 versus 72.70 ± 4.04; P = .377). However, American Orthopedic Foot and Ankle Society scores were higher in the anterolateral group than in the posterolateral group (80.43 ± 4.32 versus 75.43 ± 11.32; P = .030). CONCLUSIONS: Both the anterolateral and posterolateral approaches can achieve good results in the treatment of supination-external rotation type IV ankle fractures. Compared with the posterolateral approach, the anterolateral approach is advantageous for the treatment of supination-external rotation type IV ankle fractures given its safety and ability to reduce trauma, clear field of view revealed, and allow for exploration and repair of the inferior tibiofibular anterior syndesmosis within the same incision.

In vivo axial load-share ratio measurement using a novel hexapod system for safe external fixator removal.

BACKGROUND: External fixation is widely used in the treatment of traumatic fractures; however, orthopedic surgeons encounter challenges in deciding the optimal time for fixator removal. The axial load-share ratio (LS) of the fixator is a quantitative index to evaluate the stiffness of callus healing. This paper introduces an innovative method for measuring the LS and assesses the method's feasibility and efficacy. Based on a novel hexapod LS-measurement system, the proposed method is to improve the convenience and precision of measuring LS in vivo, hence facilitating the safe removal of external fixators. METHODS: A novel hexapod system is introduced, including its composition, theoretical model, and method for LS measurement. We conducted a retrospective study on 82 patients with tibial fractures treated by the Taylor Spatial Frame in our hospital from September 2018 to June 2020, of which 35 took LS measurements with our novel method (Group I), and 47 were with the traditional method (Group II). The external fixator was removed when the measurement outcome (LS < 10%) was consistent with the surgeon's diagnosis based on the clinical and radiological assessment (bone union achieved). RESULTS: No significant difference was found in the fracture healing time (mean 25.3 weeks vs. 24.9 weeks, P > 0.05), frame-wearing duration (mean 25.5 weeks vs. 25.8 weeks, P > 0.05), or LS measurement frequency (mean 1.1 times vs. 1.2 times, P > 0.05). The measurement system installation time in Group I was significantly shorter compared to Group II (mean 14.8 min vs. 81.3 min, P < 0.001). The LS value of the first measurement in Group I was lower than that of Group II (mean 5.1% vs. 6.9%, P = 0.011). In Group I, the refracture rate was 0, but in Group II it was 4.3% (2/47, P > 0.05). CONCLUSION: The novel hexapod LS-measurement system and involved method demonstrated enhanced convenience and precision in measuring the LS of the external fixator in vivo. The LS measurement indicates the callus stiffness of fracture healing, and is applicable to evaluate the safety of removing the fixator. Consequently, it is highly recommended for widespread adoption in clinical practice.

Comparative analysis of mechanical conditions in bone union following first metatarsophalangeal joint arthrodesis with varied locking plate positions: A finite element analysis.

BACKGROUND: First metatarsophalangeal joint arthrodesis is a typical medical treatment performed in cases of arthritis or joint deformity. The gold standard for this procedure is arthrodesis stabilisation with the dorsally positioned plate. However, according to the authors' previous studies, medially positioned plate provides greater bending stiffness. It is worth to compare the mechanical conditions for bone formation in the fracture callus for both placements of the locking plate. METHODS: Two finite element models of the first metatarsophalangeal joint with the dorsally and medially positioned plate were defined in the Abaqus software to simulate differentiation of the fracture callus. A simplified load application, i.e. one single step per each day and the diffusion of the mesenchymal stem cells into the fracture region were assumed in an iterative hardening process. The changes of the mesenchymal stem cells into different phenotypes during the callus stiffening were governed by the octahedral shear strain and interstitial fluid velocity according to Prendergast mechanoregulation theory. Basing on the obtained results the progress of the cartilage and bone tissues formation and their distribution within the callus were compared between two models. FINDINGS: The obtained results suggest that after 6 weeks of simulation the healing progress is in general comparable for both plates. However, earlier closing of external callus was observed for the medially positioned plate which had greater vertical bending stiffness. This process enables faster internal callus hardening and promotes symmetrical bridging.

Factors which can influence elastic stable intramedullary nailing removal in healed bone cysts in children.

Elastic stable intramedullary nailing (ESIN) internal fixation is used clinically to treat pathological fractures of bone cysts in children. However, one of the most important complications was removal difficulty. In this study, we aim to analyse the factors which can influence ESIN removal in healed bone cysts in children. From April 2014 to November 2020, the clinical data of 49 children who underwent elastic stable intramedullary nail removal for pathological fractures of the bone cysts in our hospital were retrospectively analysed. The following data, including age, sex, pathological fracture site, with bone graft, number of ESINs, ESIN indwelling time, and extraosseous length of ESIN were collected, and univariate analysis and logistic regression analysis was performed. The frequency of difficulty in ESIN extraction was 44.90% (22/49). The univariate logistic regression analysis showed that age,ESIN indwelling time,with bone garft and extraosseous length of ESIN may be correlated with the difficulty in removing ESIN (P < 0.05), while sex, pathological fracture site, number of ESIN may not be correlated with the difficulty in removing ESIN (P > 0.05).The multivariate logistic regression analysis showed that the ESIN indwelling time was the independent influencing factor for difficulty in removing ESIN (P < 0.05). The factors influencing the ESIN removal in healed bone cysts in children include over 11.79 years old, the long indwelling time of the ESIN(over 10.5 months),with bone graft and short extraosseous length of ESIN(≤ 0.405 cm). These factors influencing ESIN removal in healed bone cysts in children should be considered.

[Research progress in the treatment of distal humeral metaphyseal-diaphyseal junction fracture in children].

Objective: To summarize the research progress in the treatment of distal humeral metaphyseal-diaphyseal junction (DHMDJ) fractures in children and to provide reference for clinical practice. Methods: The characteristics and treatment methods of transverse and comminuted DHMDJ fractures in children were summarized and analyzed by referring to relevant literature at home and abroad. Results: DHMDJ fractures in children are not uncommon clinically, with high fracture line position, multi-directional instability, difficult closed reduction in treatment, and easy to cause complications such as coronal and sagittal deformity of the elbow. The Kirschner wire technique was effective for DHMDJ fractures with the fracture line at the middle and low levels, but was prone to iatrogenic ulnar nerve injury. Elastic stable intramedullary nail is suitable for higher-position transverse DHMDJ fractures. However, this technique requires a second operation to remove the internal fixator, and may cause iatrogenic epiphysis plate injury in children. External fixator is a new way to treat DHMDJ fractures, and it can show satisfactory results for transverse and comminuted DHMDJ fractures. However, at present, there are few relevant studies, and most of them focus on biomechanical studies, and the efficacy lacks high-quality clinical research support. Conclusion: The ultimate goal of DHMDJ fracture treatment in children is to restore the anatomical alignment of the fracture and prevent the loss of reduction. The choice of internal fixator depends on the location of the fracture line and the shape of the fracture to provide personalized treatment.

Metatarsal Fractures.

Metatarsal fractures are some of the most common fractures reported in the human body. Recent advances in surgical techniques and fixation have helped facilitate healing and improved outcomes for our patients. The treatment goals of metatarsal fractures are to maintain the metatarsal parabola, sagittal position of the metatarsal heads, and a congruent metatarsophalangeal joint. Most of these injuries can be treated nonoperatively, but displaced fractures require surgical intervention to preserve normal gait biomechanics.

Local Application of Tanshinone IIA protects mesenchymal stem cells from apoptosis and promotes fracture healing in ovariectomized mice.

BACKGROUND: Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing. METHODS: MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel. RESULTS: Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation. CONCLUSIONS: Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.

External fixator versus elastic stable intramedullary nail for treatment of metaphyseal-diaphyseal junction fractures of the pediatric distal femur: a case-control study.

BACKGROUND: Several methods have been used for the treatment of pediatric distal femoral fractures, such as elastic stable intramedullary nail (ESIN), external fixator (EF) and plate osteosynthesis, but there has been no consensus about the optimal method. The purpose of this study was to compare the clinical outcome between EF and ESIN techniques used in metaphyseal-diaphyseal junction (MDJ) fractures of the pediatric distal femur. METHODS: We retrospectively analyzed operatively treated MDJ fractures of pediatric distal femur between January 2015 and January 2022. Patient charts were reviewed for demographics, injury and data of radiography. All of the patients were divided into EF and ESIN groups according to the operation techniques. Malalignment was defined as more than 5 degrees of angular deformity in either plane. Clinical outcomes were measured by Flynn scoring system. RESULTS: Thirty-eight patients were included in this study, among which, 23 were treated with EF, and 15 with ESIN. The mean follow-up time was 18 months (12-24 months). At the final follow-up, all of the fractures were healed. Although there were no statistical differences between the two groups in demographic data, length of stay, estimated blood loss (EBL), rate of open reduction, time to fracture healing and Flynn score, the EF was superior to ESIN in operative time, fluoroscopic exposure and time to partial weight-bearing. The EF group had a significantly higher rate of skin irritation, while the ESIN had a significantly higher rate of malalignment. CONCLUSION: EF and ESIN are both effective methods in the treatment of MDJ fractures of the pediatric distal femur. ESIN is associated with lower rates of skin irritation. However, EF technique has the advantages of shorter operative time, reduced fluoroscopic exposure, and shorter time to partial weight-bearing, as well as lower incidence of malalignment. LEVEL OF EVIDENCE: Level III.

Comparison of reamer irrigator aspirator (RIA) suspension versus bone marrow aspirate concentrate (BMC) for percutaneous treatment of long bone nonunions-A preclinical canine model.

OBJECTIVE: To compare the bone healing effects of percutaneously delivered bone marrow aspirate concentrate (BMC) versus reamer irrigator aspirator (RIA) suspension in a validated preclinical canine ulnar nonunion model. We hypothesized that BMC would be superior to RIA in inducing bone formation across a nonunion site after percutaneous application. The null hypothesis was that BMC and RIA would be equivalent. METHODS: A bilateral ulnar nonunion model (n= 6; 3 matched pairs) was created. Eight weeks after segmental ulnar ostectomy, RIA from the ipsilateral femur and BMC from the proximal humerus were harvested and percutaneously administered into either the left or right ulnar defect. The same volume (3 ml) of RIA suspension and BMC were applied on each side. Eight weeks after treatment, the dogs were euthanized, and the nonunions were evaluated using radiographic, biomechanical, and histologic assessments. RESULTS: All dogs survived for the intended study duration, formed radiographic nonunions 8 weeks after segmental ulnar ostectomy, and underwent the assigned percutaneous treatment. Radiographic and macroscopic assessments of bone healing at the defect sites revealed superior bridging-callous formation in BMC-treated nonunions. Histologic analyses revealed greater amount of bony bridging and callous formation in the BMC group. Biomechanical testing of the treated nonunions did not reveal any significant differences. CONCLUSION: Bone marrow aspirate concentrate (BMC) had important advantages over Reamer Irrigator Aspirator (RIA) suspension for percutaneous augmentation of bone healing in a validated preclinical canine ulnar nonunion model based on clinically relevant radiographic and histologic measures of bone formation.

Technology Behind Cell Therapy Augmentation of Fracture Healing: Concentrated Bone Marrow Aspirate.

With an aging population, and an anticipated increase in overall fracture incidence, a sound understanding of bone healing and how technology can optimize this process is crucial. Concentrated bone marrow aspirate (cBMA) is a technology that capitalizes on skeletal stem and progenitor cells (SSPCs) to enhance the regenerative capacity of bone. This overview highlights the science behind cBMA, discusses the role of SSPCs in bone homeostasis and fracture repair, and briefly details the clinical evidence supporting the use of cBMA in fracture healing. Despite promising early clinical results, a lack of standardization in harvest and processing techniques, coupled with patient variability, presents challenges in optimizing the use of cBMA. However, cBMA remains an emerging technology that may certainly play a crucial role in the future of fracture healing augmentation.

The induced membrane technique for the management of infected segmental bone defects.

Aims: The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes. Methods: Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis. Results: Among the 203 enrolled patients, infection recurred in 27 patients (13.3%) after bone grafting. The union rate was 75.9% (154 patients) after second-stage surgery without additional procedures, and final union was achieved in 173 patients (85.2%) after second-stage surgery with or without additional procedures. The mean healing time was 9.3 months (3 to 37). Multivariate logistic regression analysis of 203 patients showed that the number (≥ two) of debridements (first stage) was an independent risk factor for infection recurrence and nonunion. Larger defect sizes were associated with higher odds of nonunion. After excluding 27 patients with infection recurrence, multivariate analysis of the remaining 176 patients suggested that intramedullary nail plus plate internal fixation, smoking, and an allograft-to-autograft ratio exceeding 1:3 adversely affected healing time. Conclusion: The IMT is an effective method to achieve infection eradication and union in the management of infected segmental bone defects. Our study identified several risk factors associated with unfavourable outcomes. Some of these factors are modifiable, and the risk of adverse outcomes can be reduced by adopting targeted interventions or strategies. Surgeons can fully inform patients with non-modifiable risk factors preoperatively, and may even use other methods for bone defect reconstruction.

Plasminogen activator inhibitor-1 is involved in glucocorticoid-induced decreases in angiogenesis during bone repair in mice.

INTRODUCTION: Glucocorticoids delay fracture healing and induce osteoporosis. Angiogenesis plays an important role in bone repair after bone injury. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. However, the mechanisms by which glucocorticoids delay bone repair remain unclear. MATERIALS AND METHODS: Therefore, we herein investigated the roles of PAI-1 and angiogenesis in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered dexamethasone (Dex). RESULTS: PAI-1 deficiency significantly attenuated Dex-induced decreases in the number of CD31-positive vessels at damaged sites 4 days after femoral bone injury in mice. PAI-1 deficiency also significantly ameliorated Dex-induced decreases in the number of CD31- and endomucin-positive type H vessels and CD31-positive- and endomucin-negative vessels at damaged sites 4 days after femoral bone injury. Moreover, PAI-1 deficiency significantly mitigated Dex-induced decreases in the expression of vascular endothelial growth factor as well as hypoxia inducible factor-1α, transforming growth factor-ß1, and bone morphogenetic protein-2 at damaged sites 4 days after femoral bone injury. CONCLUSION: The present results demonstrate that Dex-reduced angiogenesis at damaged sites during the early bone-repair phase after femoral bone injury partly through PAI-1 in mice.

The role of hematopoiesis in bone repair: an update.

PURPOSE OF REVIEW: The repair of bone after injury requires the participation of many different immune cell populations, which are derived from the hematopoietic lineage. The field of osteoimmunology, or the study of the interactions between bone and the immune system, is a growing field with emerging impact on both the basic science and clinical aspects of fracture healing. RECENT FINDINGS: Despite previous focus on the innate immune system in fracture healing, recent studies have revealed an important role for the adaptive immune system in bone repair. The composition of adaptive and innate immune cell populations present at the fracture site is significantly altered during aging and diet-induced obesity, which may contribute to delayed healing. Recent data also suggest a complicated relationship between fracture repair and systemic inflammation, raising the possibility that immune populations from distant sites such as the gut can impact the bone repair process. SUMMARY: These findings have important implications for the treatment of fracture patients with antibiotics or anti-inflammatory drugs. Furthermore, the effects of systemic inflammation on fracture repair in the contexts of aging or obesity should be carefully interpreted, as they may not be uniformly detrimental.

mPPTMP195 nanoparticles enhance fracture recovery through HDAC4 nuclear translocation inhibition.

Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations. These challenges include issues associated with autologous material donor sites, intricate preparation procedures for artificial biomaterials, suboptimal biocompatibility, and extended degradation cycles, all of which are detrimental to bone regeneration. Hence, there is an urgent need to design a novel material with a straightforward preparation method that can substantially enhance bone regeneration. In this context, we developed a novel nanoparticle, mPPTMP195, to enhance the bioavailability of TMP195 for fracture treatment. Our results demonstrate that mPPTMP195 effectively promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts while inhibiting the differentiation of bone marrow mononuclear macrophages into osteoclasts. Moreover, in a mouse femur fracture model, mPPTMP195 nanoparticles exhibited superior therapeutic effects compared to free TMP195. Ultimately, our study highlights that mPPTMP195 accelerates fracture repair by preventing HDAC4 translocation from the cytoplasm to the nucleus, thereby activating the NRF2/HO-1 signaling pathway. In conclusion, our study not only proposes a new strategy for fracture treatment but also provides an efficient nano-delivery system for the widespread application of TMP195 in various other diseases.

Identification of circulating miRNAs as fracture-related biomarkers.

Fracture non-unions affect many patients worldwide, however, known risk factors alone do not predict individual risk. The identification of novel biomarkers is crucial for early diagnosis and timely patient treatment. This study focused on the identification of microRNA (miRNA) related to the process of fracture healing. Serum of fracture patients and healthy volunteers was screened by RNA sequencing to identify differentially expressed miRNA at various times after injury. The results were correlated to miRNA in the conditioned medium of human bone marrow mesenchymal stromal cells (BMSCs) during in vitro osteogenic differentiation. hsa-miR-1246, hsa-miR-335-5p, and miR-193a-5p were identified both in vitro and in fracture patients and their functional role in direct BMSC osteogenic differentiation was assessed. The results showed no influence of the downregulation of the three miRNAs during in vitro osteogenesis. However, miR-1246 may be involved in cell proliferation and recruitment of progenitor cells. Further studies should be performed to assess the role of these miRNA in other processes relevant to fracture healing.